Multifunctional theragnostic ultrasmall gold nanodot-encapsuled perfluorocarbon nanodroplets for laser-focused ultrasound sequence irradiation (LFSI)-based enhanced tumor ablation

Despite the substantial potential of focused ultrasound therapy, its efficacy in cancer therapy has been limited due to the high cavitation threshold and safety concerns regarding the use of high-intensity energy pulses. Here, ultrasmall Au nanodot-loaded PEG-modified perfluorocarbon nanodroplets (Au-PFCnDs) were prepared and used as a therapeutic enhancer. A LFSI method was designed to achieve enhanced tumor ablation at a mild focused ultrasound (FUS) energy pulse with the assistance of the instinct photothermal effect of intratumor-permeable ultrasmall Au nanodots under 808 nm NIR laser irradiation. In addition to their therapeutic function, Au-PFCnDs can also generate multimodal images to provide information for tumor surveillance and treatment guidance. The experimental results also showed that the cRGD-targeted Au-PFCnDs could be more efficiently delivered into the tumor and selectively destroy tumors with no observable side effects on normal tissue under LFSI treatment.